This proposal will examine the effects of acute and chronic lead administration, as well as other metals, on a number of defined synaptic inputs, and transmitters to identified neurons in hippocampus, cerebral cortex, cerebellum and caudate. The effect of fetal and neonatal lead exposure on maturation of these same brain regions, studied using histological, histochemical and electrophysiological techniques, will also be examined. All experiments will be carried out in brain pieces transplanted to the anterior chamber of the eye, permitting an isolated and selective activation of the various inputs to mature brain as well as an analysis of intrinsic vs. extrinsic or indirect factors in any lead-induced developmental abnormalities. Catecholamine-containing brainstem nuclei will be sequentially grafted to the anterior chamber before and after hippocampus, cerebellum, cerebral cortex or caudate. Isolated brain circuits upon which to test the effects of lead may thus be produced using these double transplants.